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Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells

Kirkham, Frances; Pera, Alejandra; Simanek, Amanda M.; Bano, Aalia; Morrow, George; Reus, Bernhard; Caserta, Stefano; Smith, Helen E.; Davies, Kevin A; Rajkumar, Chakravarthi; Kern, Florian

Authors

Frances Kirkham

Alejandra Pera

Amanda M. Simanek

Aalia Bano

George Morrow

Bernhard Reus

Helen E. Smith

Kevin A Davies

Chakravarthi Rajkumar

Florian Kern



Abstract

Human Cytomegalovirus (CMV) infection is associated with atherosclerosis, higher cardiovascular disease (CVD) risk, and an increase in memory T-cells (Tmem). T-cells have also been implicated in CVD, independently of CMV infection. To better understand the CMV-associated CVD risk, we examined the association between CMV (IgG) serostatus and central aortic (carotid-to-femoral) pulse wave velocity (cfPWV), an early, independent predictor of CVD. We also investigated if such an association might be reflected by the distribution of Tmem and/or other T-cell subsets.

Methods: Healthy older volunteers (60-93 years) underwent routine clinical and laboratory evaluation, including assessment of cfPWV in eligible participants. Flow-cytometry was used to assess proportions of memory T-cells, CD28null T-cells, and CMV-specific T-cells. The following associations were examined; CMV serostatus/cfPWV, CMV serostatus/proportion of Tmem, proportion of Tmem/cfPWV, CD28null T-cells/cfPWV, and CMV-specific T-cells/cfPWV. Linear regression models were used to adjust for age, sex, socioeconomic status, smoking, waist-to-hip ratio, cholesterol, and blood pressure as required.

Results: Statistically significant positive associations were found (P-values for the fully adjusted models are given); CMV serostatus/cfPWV in men (P ≤ 0.01) but not in women, CMV serostatus/proportions of CD4 Tmem in men (P ≤ 0.05) but not in women; proportions of CD4 Tmem/cfPWV among CMV seropositive (CMV+) people (P ≤ 0.05) but not CMV seronegative (CMV-) people.

Conclusion: CMV infection increases the CVD risk of older men by increasing cfPWV. This may be mediated in part by increased proportions of CD4 Tmem, higher numbers of which are found in CMV+ older people and more so among men than women. Given the high prevalence of CMV worldwide, our findings point to a significant global health issue. Novel strategies to mitigate the increased CVD risk associated with CMV may be required.

Citation

Kirkham, F., Pera, A., Simanek, A. M., Bano, A., Morrow, G., Reus, B., Caserta, S., Smith, H. E., Davies, K. A., Rajkumar, C., & Kern, F. (in press). Cytomegalovirus infection is associated with an increase in aortic stiffness in older men which may be mediated in part by CD4 memory T-cells. Theranostics, 11(12), 5728-5741. https://doi.org/10.7150/thno.58356

Journal Article Type Article
Acceptance Date Mar 7, 2021
Online Publication Date Mar 31, 2021
Deposit Date Apr 7, 2021
Publicly Available Date Apr 13, 2021
Journal Theranostics
Electronic ISSN 1838-7640
Publisher Ivyspring International Publisher
Peer Reviewed Peer Reviewed
Volume 11
Issue 12
Pages 5728-5741
DOI https://doi.org/10.7150/thno.58356
Keywords Central aortic stiffness; Pulse wave velocity; Cardiovascular risk; Human Cytomegalovirus (CMV); Memory T-cells
Public URL https://hull-repository.worktribe.com/output/3746715

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Copyright Statement
© The author(s). This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/).
See http://ivyspring.com/terms for full terms and conditions.






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